These clinical relationships between tobacco use and depression do suggest some important effects of nicotine and nicotinic receptor mechanisms in major depressive disorder. Thus, it has been postulated that nicotine and cigarette smoking may exert antidepressant effects [4, 5, 11, 12], presumably mediated through stimulation of nicotinic acetylcholine receptor (nAChR) systems. In fact, it has been shown in an open-label trial that nicotine patch could produce substantial antidepressant effects with 3 days of transdermal nicotine administration in non-smoking subjects with major depression [12].